Cough
Conditions
Brief summary
The objectives of this pivotal study are: 1. to evaluate bioavailability of an extended-release and immediate release Codeine Phosphate/Guaifenesin tablet at steady state following multiple oral administration 2. to assess the safety and tolerability of this Codeine Phosphate/Guaifenesin extended release formulation.
Detailed description
This study will be a single-center, Two-site open-label, randomized, multiple-dose, two-treatment, two-period crossover design. During the course of the study, thirty eight (38) healthy adult volunteers will receive multiple doses of Codeine Phosphate/ Guaifenesin extended-release tablet 30 mg/600 mg and multiple doses of an IR Codeine Phosphate/ Guaifenesin immediate-release tablet 20 mg/400 mg tablet in two separate treatment periods. Volunteers will enter the clinic the day prior \[approximately 12 hours\] to each dosing and will be confined in the clinic for 7 nights for each treatment period. The extended release tablet (test) will be administered as two tablets two times a day, 12 hours apart, and the immediate release tablet (reference) will be administered as one tablet six times a day, 4 hours apart. Pre-dose blood samples will be collected prior to morning dose on Days 1, 2, 3, 4, 5, 6 and 7. On Day 7, Two extended release tablets will be given once in the morning and the immediate release tablet will be given three times, in the morning and 4 and 8 hours later. Serial blood samples will be collected on Day 7 for up to 12 hours post morning dose. On Day 7 volunteers will be released from the study site after the 12-hour blood collection if clinically appropriate and will return to the study site to start the next treatment after a minimum of 7 days of wash-out period, which begins the morning after the last dose taken of the previous Period.
Interventions
DRUGCodeine Phosphate/Guaifenesin ER Tablet
Provide two Codeine Phosphate and Guaifenesin ER Tablet every 12 hours for 6 1/2 days.
DRUGCodeine Phosphate/Guaifenesin IR Tablet
Provide one Codeine Phosphate and Guaifenesin IR Tablet every 4 hours for 6 1/2 days
Sponsors
Pharmaceutical Research Unit, Jordan
Nexgen Pharma, Inc
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy non-smoking volunteers (Female volunteers on a stable contraceptive medication regimen (\> 3 months) may continue during the course of the study but its use must be documented), 18 to 45 years of age, inclusive; Ethnic Group: Arab & Mediterranean. * Race: Mixed skin (white & black skin people). * Body Mass Index (BMI) between 18 and 32 kg/m2, inclusive (minimum of 50 kg weight); * willing and able to comply with the appropriate instructions necessary to complete the study, and; * Fully informed of the risks of entering the study and willing to provide written informed consent. * Subject is available for the whole study period and gave written informed consent * If female, must be practicing abstinence or using a medically acceptable form of contraception (e.g., intrauterine device, hormonal birth control \[continuously used for at least 3 months before first dose\], or double barrier method). For the purpose of this study, all females are considered to be of childbearing potential unless they have been post - menopausal, biologically sterile, or surgically sterile (i.e., hysterectomy, bilateral oophorectomy, or tubal ligation) for more than one (1) year * Normal Physical examination. * Vital signs within normal ranges. * All laboratory screening results within the normal range, or being assessed as clinically Non-significant by the attending physician. * Normal Kidney and Liver functions test.
Exclusion criteria
* • Women of childbearing potential who don't use any contraceptive method, pregnant and/or lactating women. * Ethnic Group (Non- Arab &/ or Non- Mediterranean) * A significant abnormality in the pre-study physical examination that would place the volunteer at risk during participation in the trial; * A clinical laboratory test value outside of the accepted reference range that is deemed by the Investigator to be clinically significant; * Require prescription medication on a regular basis; * A clinically significant illness during the 28 days prior to Period 1 dosing (as determined by the Investigator); * History of serious illness that can impact fate of drugs * History of gastrointestinal obstruction, constipation, inflammatory bowel disease, gallbladder disease, pancreas disorder over last 2 years, or recent (over last 3 years) gastrointestinal tract surgery, including gall bladder resection; * Known history or presence of cardiac, pulmonary, endocrine, musculoskeletal, neurological, hematological or disease. * Subjects with acute pulmonary insufficiency, respiratory depression, acute or chronic severe respiratory insufficiency or history of any of these * History of head injury, seizures over last 4 years deemed by the Investigator to be clinically significant; * Mental disease * History of kidney disease or urination problem over last 2 years deemed by the Investigator to be clinically significant * Subjects with renal and/or hepatic insufficiency should be excluded * Presence of any significant physical or organ abnormality * History of low blood pressure is deemed by the Investigator to be clinically significant; * A positive Hepatitis B surface antigen, Hepatitis C antibody screen, or a reactive HIV antibody screen; * Known or suspected hypersensitivities, allergies, or other contraindications to Codeine or a related opioid and/or Guaifenesin; * History of severe allergy or allergic reactions to study drug or related drugs or heparin * Known history or presence of food allergies, or any condition known to interfere with the absorption, distribution, metabolism or excretion of drugs * Known or suspected history of drug abuse within lifetime as judged by the Investigator; * History of alcohol abuse or excessive intake of alcohol within last 5 years as judged by the Investigator; * Positive screen for drugs of abuse, alcohol, or cotinine (nicotine) at screening or on admission to the unit prior to administration of investigational products; * Use of drugs that induce or inhibit the hepatic metabolizing cytochrome P450 2D6 enzymes, within 30 days prior to administration of study formulations. Examples of inducers include: piperidins, carbamazepine, dexamethasone, rifampin. Examples of inhibitors include: cimetidine, diphenhydramine, fluvastatine, methadone, and ranitidine; * Use of prescription medications within 21 days and OTC medications (including vitamins or herbal products) within 7 days (excluding flu vaccination) prior to the first administration of the study medication without Sponsor approval; * Intake of Alcohol 48 before each study drug administration, and caffeine, or xanthine beverages 24 hrs before each study drug administration. * Use of any investigational drug within 30 days prior to first dosing; * Use of any tobacco-containing product within 6 months of first dosing; * Donated more than 400 mL of blood within 4 weeks before first dosing; * Participation in another bioequivalence study and/or Clinical trials within 80 days prior to the start of this study Period I * Exhausting physical exercise in the last 48 hours (e.g. weight lifting) or any recent significant change in dietary or exercise habits. * Abnormal vital signs * Abnormal Kidney and Liver functions test. * In the opinion of the Investigator, unlikely or unable to successfully complete the study; * Volunteer is vegetarian. * Vomiting, Diarrhea on admission.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak Plasma Concentration (Cmax) | One week | Determination peak plasma concentration of each active ingredient during 12 hours following six days of dosing |
| Area under the plasma concentration versus time curve (AUC) | One week | Determination of total area under the plasma concentration versus time curve (AUC) during the 12 hours following 6 days of dosing. |
Countries
Jordan
Outcome results
None listed